ID CD63_HUMAN Reviewed; 238 AA. AC P08962; Q5TZP3; Q9UCG6; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 22-FEB-2012, entry version 124. DE RecName: Full=CD63 antigen; DE AltName: Full=Granulophysin; DE AltName: Full=Lysosomal-associated membrane protein 3; DE Short=LAMP-3; DE AltName: Full=Melanoma-associated antigen ME491; DE AltName: Full=OMA81H; DE AltName: Full=Ocular melanoma-associated antigen; DE AltName: Full=Tetraspanin-30; DE Short=Tspan-30; DE AltName: CD_antigen=CD63; GN Name=CD63; Synonyms=MLA1, TSPAN30; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=88210273; PubMed=3365686; RA Hotta H., Ross A.H., Huebner K., Isobe M., Wendeborn S., Chao M.V., RA Ricciardi R.P., Tsujimoto Y., Croce C.M., Koprowski H.; RT "Molecular cloning and characterization of an antigen associated with RT early stages of melanoma tumor progression."; RL Cancer Res. 48:2955-2962(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Ovary; RX MEDLINE=91025550; PubMed=2171551; DOI=10.1089/dna.1990.9.479; RA Rapp G., Freudenstein J., Klaudiny J., Mucha J., Wempe F., Zimmer M., RA Scheit K.H.; RT "Characterization of three abundant mRNAs from human ovarian granulosa RT cells."; RL DNA Cell Biol. 9:479-485(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION. RX MEDLINE=91131632; PubMed=1993697; RA Metzelaar M.J., Wigngaard P.L., Peters P.J., Sixma J.J., RA Nieuwenhuis H.K., Clevers H.C.; RT "CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a RT screening procedure for intracellular antigens in eukaryotic cells."; RL J. Biol. Chem. 266:3239-3245(1991). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=92181348; PubMed=1339263; RA Wang M.X., Earley J.J. Jr., Shields J.A., Donoso L.A.; RT "An ocular melanoma-associated antigen. Molecular characterization."; RL Arch. Ophthalmol. 110:399-404(1992). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=92287132; PubMed=1599482; DOI=10.1016/S0006-291X(05)81004-6; RA Hotta H., Miyamoto H., Hara I., Takahashi N., Homma M.; RT "Genomic structure of the ME491/CD63 antigen gene and functional RT analysis of the 5'-flanking regulatory sequences."; RL Biochem. Biophys. Res. Commun. 185:436-442(1992). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skeletal muscle; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PROTEIN SEQUENCE OF 2-38, SUBCELLULAR LOCATION, AND LACK OF EXPRESSION RP IN HERMANSKY-PUDLAK SYNDROME. RC TISSUE=Platelet; RX MEDLINE=93232306; PubMed=7682577; DOI=10.1172/JCI116388; RA Nishibori M., Cham B., McNicol A., Shalev A., Jain N., Gerrard J.M.; RT "The protein CD63 is in platelet dense granules, is deficient in a RT patient with Hermansky-Pudlak syndrome, and appears identical to RT granulophysin."; RL J. Clin. Invest. 91:1775-1782(1993). RN [12] RP PROTEIN SEQUENCE OF 2-21. RX MEDLINE=86049405; PubMed=4062294; DOI=10.1016/0003-9861(85)90241-3; RA Ross A.H., Dietzschold B., Jackson D.M., Earley J.J., Ghrist B.F.D., RA Atkinson B., Koprowski H.; RT "Isolation and amino terminal sequencing of a novel melanoma- RT associated antigen."; RL Arch. Biochem. Biophys. 242:540-548(1985). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=10793155; RA Kobayashi T., Vischer U.M., Rosnoblet C., Lebrand C., Lindsay M., RA Parton R.G., Kruithof E.K.O., Gruenberg J.; RT "The tetraspanin CD63/lamp3 cycles between endocytic and secretory RT compartments in human endothelial cells."; RL Mol. Biol. Cell 11:1829-1843(2000). RN [14] RP GLYCOSYLATION AT ASN-130. RX MEDLINE=22660472; PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [15] RP SUBCELLULAR LOCATION. RX PubMed=15351990; DOI=10.1002/cyto.a.20068; RA Gruetzkau A., Smorodchenko A., Lippert U., Kirchhof L., Artuc M., RA Henz B.M.; RT "LAMP-1 and LAMP-2, but not LAMP-3, are reliable markers for RT activation-induced secretion of human mast cells."; RL Cytometry 61:62-68(2004). RN [16] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RC TISSUE=Placenta; RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x; RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., RA Schaefer H., Elsaesser H.-P., Mann M., Hasilik A.; RT "Integral and associated lysosomal membrane proteins."; RL Traffic 8:1676-1686(2007). RN [17] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130, AND MASS RP SPECTROMETRY. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). CC -!- FUNCTION: This antigen is associated with early stages of melanoma CC tumor progression. May play a role in growth regulation. CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC Lysosome membrane; Multi-pass membrane protein. Late endosome CC membrane; Multi-pass membrane protein. Note=Also found in Weibel- CC Palade bodies of endothelial cells. Located in platelet dense CC granules. CC -!- TISSUE SPECIFICITY: Dysplastic nevi, radial growth phase primary CC melanomas, hematopoietic cells, tissue macrophages. CC -!- MISCELLANEOUS: Lack of expression of CD63 in platelets has been CC observed in a patient with Hermansky-Pudlak syndrome (HPS). CC Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, CC rare, autosomal recessive disorder characterized by oculocutaneous CC albinism, bleeding due to platelet storage pool deficiency, and CC lysosomal storage defects. This syndrome results from defects of CC diverse cytoplasmic organelles including melanosomes, platelet CC dense granules and lysosomes. Ceroid storage in the lungs is CC associated with pulmonary fibrosis, a common cause of premature CC death in individuals with HPS. CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07982; CAA30792.1; -; mRNA. DR EMBL; M59907; AAA63235.1; -; mRNA. DR EMBL; M58485; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; S93788; AAB21617.1; -; mRNA. DR EMBL; X62654; CAA44519.1; -; Genomic_DNA. DR EMBL; AK311893; BAG34834.1; -; mRNA. DR EMBL; CR542096; CAG46893.1; -; mRNA. DR EMBL; BT007073; AAP35736.1; -; mRNA. DR EMBL; BT020137; AAV38939.1; -; mRNA. DR EMBL; BT020138; AAV38940.1; -; mRNA. DR EMBL; CH471054; EAW96827.1; -; Genomic_DNA. DR EMBL; BC002349; AAH02349.1; -; mRNA. DR EMBL; BC013017; AAH13017.1; -; mRNA. DR IPI; IPI00215998; -. DR PIR; I38016; I38016. DR RefSeq; NP_001771.1; NM_001780.4. DR UniGene; Hs.445570; -. DR ProteinModelPortal; P08962; -. DR IntAct; P08962; 9. DR MINT; MINT-2981823; -. DR STRING; P08962; -. DR DMDM; 116026; -. DR PRIDE; P08962; -. DR Ensembl; ENST00000257857; ENSP00000257857; ENSG00000135404. DR GeneID; 967; -. DR KEGG; hsa:967; -. DR UCSC; uc001shm.1; human. DR CTD; 967; -. DR GeneCards; GC12M056119; -. DR H-InvDB; HIX0010704; -. DR HGNC; HGNC:1692; CD63. DR HPA; CAB026356; -. DR HPA; HPA010088; -. DR MIM; 155740; gene. DR neXtProt; NX_P08962; -. DR eggNOG; NOG268658; -. DR GeneTree; ENSGT00640000091134; -. DR HOGENOM; HBG716506; -. DR HOVERGEN; HBG107306; -. DR InParanoid; P08962; -. DR KO; K06497; -. DR OMA; EFNKDFR; -. DR OrthoDB; EOG4HX51Z; -. DR PhylomeDB; P08962; -. DR Reactome; REACT_604; Hemostasis. DR NextBio; 4044; -. DR ArrayExpress; P08962; -. DR Bgee; P08962; -. DR CleanEx; HS_CD63; -. DR Genevestigator; P08962; -. DR GermOnline; ENSG00000135404; Homo sapiens. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005765; C:lysosomal membrane; TAS:ProtInc. DR GO; GO:0031088; C:platelet dense granule membrane; TAS:Reactome. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome. DR InterPro; IPR018499; Tetraspanin. DR InterPro; IPR018503; Tetraspanin_CS. DR InterPro; IPR008952; Tetraspanin_EC2. DR InterPro; IPR000301; Tetraspanin_subgr. DR Pfam; PF00335; Tetraspannin; 1. DR PRINTS; PR00259; TMFOUR. DR SUPFAM; SSF48652; Tetraspanin; 1. DR PROSITE; PS00421; TM4_1; 1. PE 1: Evidence at protein level; KW Cell membrane; Complete proteome; Direct protein sequencing; Endosome; KW Glycoprotein; Lysosome; Membrane; Reference proteome; Transmembrane; KW Transmembrane helix. FT INIT_MET 1 1 Removed. FT CHAIN 2 238 CD63 antigen. FT /FTId=PRO_0000219216. FT TOPO_DOM 2 11 Cytoplasmic (Potential). FT TRANSMEM 12 32 Helical; (Potential). FT TOPO_DOM 33 51 Extracellular (Potential). FT TRANSMEM 52 72 Helical; (Potential). FT TOPO_DOM 73 81 Cytoplasmic (Potential). FT TRANSMEM 82 102 Helical; (Potential). FT TOPO_DOM 103 203 Extracellular (Potential). FT TRANSMEM 204 224 Helical; (Potential). FT TOPO_DOM 225 238 Cytoplasmic (Potential). FT CARBOHYD 130 130 N-linked (GlcNAc...). FT CARBOHYD 150 150 N-linked (GlcNAc...) (Potential). FT CARBOHYD 172 172 N-linked (GlcNAc...) (Potential). FT CONFLICT 36 36 Q -> E (in Ref. 11; AA sequence). SQ SEQUENCE 238 AA; 25637 MW; 85AC8E235C6E425F CRC64; MAVEGGMKCV KFLLYVLLLA FCACAVGLIA VGVGAQLVLS QTIIQGATPG SLLPVVIIAV GVFLFLVAFV GCCGACKENY CLMITFAIFL SLIMLVEVAA AIAGYVFRDK VMSEFNNNFR QQMENYPKNN HTASILDRMQ ADFKCCGAAN YTDWEKIPSM SKNRVPDSCC INVTVGCGIN FNEKAIHKEG CVEKIGGWLR KNVLVVAAAA LGIAFVEVLG IVFACCLVKS IRSGYEVM //